Thyroid hormone receptor beta-1 (TRβ1) (TRβ1)

Thyroid hormone receptor beta-1 (THRβ-1) is a nuclear receptor that functions as a ligand-activated transcription factor, primarily mediating the metabolic actions of triiodothyronine (T3) in the liver (UniProt P10828). It plays a pivotal role in regulating hepatic lipid metabolism, cholesterol homeostasis, and bile acid synthesis by controlling the expression of genes such as the LDL receptor and sterol regulatory element-binding protein (SREBP-1c) (PubMed: 31054229). While the THRα isoform is predominantly expressed in the heart and bone, THRβ-1 is the major isoform in hepatic tissue, making it a high-value target for treating metabolic disorders (PubMed: 24635515). Selective THRβ agonists, such as the FDA-approved resmetirom, are designed to leverage this tissue distribution to reduce hepatic fat accumulation and improve lipid profiles in patients with metabolic dysfunction-associated steatohepatitis (MASH) (FDA: Rezdiffra Label). By avoiding THRα activation, these drugs aim to provide metabolic benefits without the risks of tachycardia, arrhythmia, or bone mineral density loss typically associated with hyperthyroidism (PubMed: 30355301).

Other names

THRB1Nuclear receptor subfamily 1 group A member 2NR1A2ERBA2TR-beta-1c-erbA-2THR-beta-1

Selective agonism of the thyroid hormone receptor beta isoform to stimulate hepatic fatty acid oxidation and cholesterol clearance while minimizing alpha-isoform-mediated cardiac and skeletal effects.